Department of Neuropathology, Institute for Pathology, Medical Faculty Carl Gustav Carus, D-01307 Dresden, Germany.
Oncol Rep. 2011 Jul;26(1):13-21. doi: 10.3892/or.2011.1265. Epub 2011 Apr 15.
Gliomas of WHO grades III-IV are malignant brain tumors mostly resistant to conventional therapies. Therefore, novel strategies for the treatment of gliomas are warranted. Although immunotherapy is gaining increased attention for the treatment of malignant gliomas and in particular of glioblastoma multiforme (GBM), this approach requires the identification of appropriate antigens. Our aim was to investigate the expression of the prostate stem cell antigen (PSCA), a highly N-glycosylated phosphatidylinositol (GPI)-anchored cell surface protein, in gliomas of different WHO grades in order to evaluate its potential as a diagnostic marker and as a target for immunotherapy. Tumor specimens and controls were assessed by quantitative RT-PCR, Western blotting and immunohistochemistry. The samples investigated in the study consisted of 210 human glial tumors, among which 31 were oligodendrogliomas, 9 ependymomas and 170 were astrocytomas (including 134 glioblastomas). PSCA was absent in normal brain tissue, but was detected in WHO grade III-IV gliomas. Weak PSCA protein expression was also recognized in some WHO grade I and WHO grade II tumors. The difference between WHO grade I-II tumors and WHO grade III-IV tumors was statistically significant (p<0.001). Our results suggest that increased PSCA expression levels are linked to gliomas of WHO grades III and IV, and may represent a suitable additional target for immunotherapy of gliomas.
WHO 分级 III-IV 级的神经胶质瘤是主要对常规治疗具有抗性的恶性脑肿瘤。因此,需要有新的策略来治疗神经胶质瘤。尽管免疫疗法在治疗恶性神经胶质瘤,特别是多形性胶质母细胞瘤(GBM)方面越来越受到关注,但这种方法需要确定合适的抗原。我们的目的是研究前列腺干细胞抗原(PSCA)在不同 WHO 分级的神经胶质瘤中的表达情况,以评估其作为诊断标志物和免疫治疗靶点的潜力。通过定量 RT-PCR、Western blotting 和免疫组织化学检测肿瘤标本和对照。本研究共调查了 210 例人类神经胶质瘤,其中 31 例为少突胶质细胞瘤,9 例为室管膜瘤,170 例为星形细胞瘤(包括 134 例胶质母细胞瘤)。PSCA 在正常脑组织中不存在,但在 WHO 分级 III-IV 级神经胶质瘤中检测到。一些 WHO 分级 I 和 II 级肿瘤也检测到了 PSCA 蛋白的弱阳性表达。WHO 分级 I-II 级肿瘤和 WHO 分级 III-IV 级肿瘤之间的差异具有统计学意义(p<0.001)。我们的结果表明,PSCA 表达水平的增加与 WHO 分级 III 和 IV 的神经胶质瘤有关,可能是神经胶质瘤免疫治疗的一个合适的附加靶点。